Summary: Our lab has analyzed the phenotype, location and functional properties of lymphocytes stimulated to produce antibodies and cytokines when challenged with vaccines, conventional protein-based antigens, and DNA derived from bacteria or viruses. This work includes studies examining the immunogenicity of the envelope glycoprotein of HIV and the protective antigen from anthrax. Also studied was the effect of adjuvants on the activation of cytokine producing cells, and whether early changes in the cytokine milieu effect subsequent immune responses. In these experiments, cells were obtained from mice immunized with specific protein antigens or vaccines. The number and specificity of antigen-specific responding cells was then monitored. In some experiments, animals were challenged with infectious pathogens, and protection monitored. This work established how changes to the CpG content of DNA vaccines alters the immunogenicity of the resultant vaccine. Data suggest that adding more CpG motifs, and insuring that they do not lie near "suppressive motifs", positively influences immunogenicity. We are in the process of establishing that use of CpG ODN in conjunction with rPA and AVA boost both the titer and avidity of the host's response to anthrax.